Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum

Eur J Pharmacol. 2002 Sep 27;452(1):105-9. doi: 10.1016/s0014-2999(02)02300-2.

Abstract

The mechanism underlying orexin-induced contraction was examined in isolated preparations of guinea pig ileum, in relation to cholinergic transmission. Orexin-A caused contraction of ileal strips in a concentration-dependent manner. 1-(2-Methylbenzoxazol-6-yl)-3-[1,5]napthyridin-4-yl-urea hydrochloride (SB-334867-A) antagonized the orexin-A-induced contraction, with no effects on the acetylcholine-induced contraction and twitch contractions. The orexin-A-induced contraction was inhibited by tetrodotoxin and atropine, but not by hexamethonium, an antagonist of vasoactive intestinal peptide and a mixture of 5-hydroxytryptamine receptor antagonists. Orexin-A evoked an outflow of [3H]acetylcholine from the ileal strips preincubated with [3H]choline, in a concentration-dependent manner, and the orexin-A-evoked outflow was inhibited by tetrodotoxin, indicating that the outflow of [3H]acetylcholine originates from the nerve terminals. The orexin-A-evoked outflow of [3H]acetylcholine was antagonized by SB-334867-A. Thus, orexin-A evokes the release of acetylcholine from the enteric cholinergic neurons due to stimulation of the orexin-1 receptors and then causes contractions of guinea pig ileum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Atropine / pharmacology
  • Benzoxazoles / pharmacology
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / pharmacology*
  • Enteric Nervous System / drug effects
  • Female
  • Ganglionic Blockers / pharmacology
  • Guinea Pigs
  • Hexamethonium / pharmacology
  • Ileum / drug effects*
  • Ileum / innervation
  • Ileum / metabolism
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Muscarinic Antagonists / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / innervation
  • Muscle, Smooth / metabolism
  • Naphthyridines
  • Neurons / physiology*
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / pharmacology*
  • Orexin Receptors
  • Orexins
  • Parasympathetic Nervous System / physiology*
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / drug effects
  • Tetrodotoxin / pharmacology
  • Urea / analogs & derivatives*
  • Urea / pharmacology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Carrier Proteins
  • Ganglionic Blockers
  • Intracellular Signaling Peptides and Proteins
  • Muscarinic Antagonists
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Hexamethonium
  • Tetrodotoxin
  • Atropine
  • Urea
  • Acetylcholine